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J Dermatol Sci. 2007 Jan;45(1):23-30. Epub 2006 Nov 22.

Roles for IL-1 and TNFalpha in dynamic behavioral responses of Langerhans cells to topical hapten application.

Author information

1
Department of Dermatology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.

Abstract

BACKGROUND:

To understand the behavioral biology of Langerhans cells (LCs), we recently recorded time-lapse images of LCs in the knock-in mice expressing the I-Abeta chain tagged with the enhanced green fluorescence protein (EGFP). EGFP(+) LCs showed relatively limited motility in the steady state, whereas topical application of dinitrofluorobenzene (DNFB) markedly augmented a unique movement of dendrites characterized by rhythmic extension and retraction, termed dSEARCH, and triggered amoeba-like lateral migration of cell bodies.

OBJECTIVE:

To define underlying mechanisms by which hapten treatment alters LC behaviors.

METHODS:

The I-Abeta-EGFP mice received subcutaneous (s.c.) injection of recombinant IL-1alpha or TNFalpha (50 ng/animal) and dynamic behaviors of EGFP(+) LCs were recorded by time-lapse confocal microscopy at several time points to measure their dSEARCH activities and lateral migration. In a different set of experiments, IL-1 receptor antagonist (IL-1Ra) or soluble TNF receptor-2 (sTNFR2) (0.5 microg/animal) was s.c. injected into the ear skin 30 min before topical application of DNFB, and LC behaviors analyzed 30 h later.

RESULTS:

Local injection of IL-1alpha or TNFalpha induced significant, albeit modest, augmentation of both dSEARCH and lateral migration. Co-injection of TNFalpha and IL-1alpha further exacerbated motile activities in a synergistic manner by similar magnitudes observed after DNFB application. Conversely, DNFB-induced behavioral changes were inhibited completely by local injection of IL-1Ra or sTNFR2.

CONCLUSION:

IL-1 and TNFalpha serve as equally important mediators of hapten-induced alteration of LC behaviors. Motile activities of epidermal LCs are reprogrammed by selected cytokines known to be produced by keratinocytes under pathological conditions.

PMID:
17123788
PMCID:
PMC1850973
DOI:
10.1016/j.jdermsci.2006.10.003
[Indexed for MEDLINE]
Free PMC Article

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